Is CTC1 p.Val263Met (c.787G>A) pathogenic?

CTC1 p.Val263Met (c.787G>A) is classified Uncertain significance in CTC1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-12-30). AlphaMissense: likely pathogenic (0.7613); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with CTC1 p.Val263Met (c.787G>A)?

CTC1 p.Val263Met (c.787G>A) is associated with Inborn genetic diseases, dyskeratosis congenita (ClinVar).

How common is CTC1 p.Val263Met (c.787G>A) in the general population?

CTC1 p.Val263Met (c.787G>A) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CTC1 p.Val263Met (c.787G>A)?

AlphaMissense predicts likely pathogenic (score 0.7613) — an in-silico prediction, not a clinical call.

CTC1 p.Val263Met

c.787G>A · rs1010062693 · VCV2325151

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.7613 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7613	likely pathogenic · top 8% in CTC1
REVEL	0.5	indeterminate
SaProt	LLR -10.57	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 2.6, phastCons 0.99
Regional constraint	o/e 0.96	unconstrained · MANE · 20 kb · p 0.088 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,980 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000558% 9/1,613,928 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,980
Finnishnot grpmax-eligible	0.00156%	64,004
African / African-American	0.00134%	74,874
South Asian	0.0011%	91,070
European (non-Finnish)	0.000424%	236,003

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CTC1
Protein: p.Val263Met
Coding: c.787G>A
MANE Select: NM_025099
dbSNP: rs1010062693
Type: single nucleotide variant
Location: chr17:8237380 (GRCh38)
Gene constraint: LOEUF 0.776 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.01 · 7 PDB
Residue 263: a β-strand

Full CTC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dyskeratosis congenita

Similar variants

CTC1 p.Val263Leu Uncertain significance ★ ⚠ same residue
CTC1 c.1617+5G>T Pathogenic/Likely pathogenic ★★ same condition
CTC1 c.1818+1G>A Likely pathogenic ★★ same condition
CTC1 c.2386-1G>A Likely pathogenic ★★ same condition
CTC1 c.2758+1G>T Pathogenic/Likely pathogenic ★★ same condition
CTC1 c.3221+1G>A Likely pathogenic ★★ same condition
CTC1 p.Ala227Val Pathogenic ★★ same condition
CTC1 p.Arg108Ter Pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ctc1-p-val263met (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown